[How much do patients know about the possible physical consequences of their eating disorder?]. / Onderzoek naar de kennis van patiënten over de mogelijke lichamelijke gevolgen van hun eetstoornis.

BACKGROUND: A lack of knowledge about the physical consequences of an eating disorder can be a sign that the patient either denies that there is a problem or minimises the problem; this can result in the patient being reluctant or unwilling to be treated. AIM: To find out how much patients know about the possible physical consequences of (or the risks involved in) their eating disorder and to check whether they know considerably more after some psycho-education. METHOD: Sixty-six female patients completed a questionnaire shortly after being admitted to a specialised eating-disorder unit and 44 patients completed the same questionnaire after about a month. In the intervening period patients received some psycho-education about the possible physical consequences of eating disorders. The psycho-education took the form of an interactive group session and a brochure of information. RESULTS: In general, the patients' knowledge about possible consequences of their illness was reasonably satisfactory (on average, 14 out of 20 questions were correct), although a considerable number of patients answered 11 questions with 'I don't know'. In the second round there was a considerable decrease in the number of 'I don't know' answers, showing that after a month patients' knowledge had improved (17 out of 20 patients now gave positive answers); the answers were independent of the type of eating disorder. One question in particular elicited the largest number of uncertain or incorrect answers, even in the second round; the question was: Can a woman who has never menstruated become pregnant?' CONCLUSION: It is advisable to assess, in a systematic way, whether patients have adequate knowledge about the physical consequences of an eating disorder. Gaps in patients' knowledge or misunderstandings can then serve as a starting point for a specific type of psycho-education.

[Pathological hoarding by children and adolescents]. / Pathologisch verzamelen bij kinderen en jeugdigen.

BACKGROUND: There is a dearth of knowledge and understanding concerning hoarding by children and adolescents. Psychiatrists need to know more about the phenomenon of hoarding since it can be a marker of psychopathology and it sometimes is symptomatic of a psychiatric disorder. AIM: To review hoarding from an epidemiological and psychopathological perspective and to discuss it in relation to the developmental aspect of the first object acquisition: the transitional object. METHOD: We conducted a literature search in PubMed, Medline, PsycINFO and the Cochranedatabase using primarily the search term 'hoarding', but also in combination with the terms: primates, child, adolescent, psych*, klepto*, transitional object, obsessive-compulsive disorder, collecting and attachment. RESULTS: Both animals and humans engage frequently in collecting and hoarding. Up to 60% of normally functioning children and adolescents are involved in collecting. A strong emotional attachment to possessions may be a response to an attachment problem. Hoarding combined with psychopathology is seen in persons of all ages but the prevalence rates for children and adults are unknown. CONCLUSION: Hoarding is a worrisome type of behaviour which must be regarded as an indication of serious comorbid psychopathology. It can occur either as a symptom of an existing disorder or as a separate disorder. Finally we recommend that hoarding be included in the diagnostic criteria of the dsm and icd.

A web-based survey of reproductive awareness and choices in women with endometriosis.

OBJECTIVE: Our aim was to study fertility issues, attitudes towards reproductive techniques and fertility preservation options in women of reproductive age with endometriosis. STUDY DESIGN: In 2018 we conducted a web-based survey on fertility issues in women aged 18-40 years with endometriosis. Participants were recruited via advertisements on social media and local endometriosis support groups. Participants completed a self-developed online questionnaire evaluating the following dimensions: sociodemographic, medical data, parental project, knowledge and attitudes toward endometriosis and fertility, means used to access information, and reproductive choices. RESULTS: The majority of women (96 %) worried about the impact of endometriosis on their fertility. Approximately half of them (52 %) reported having received sufficient information concerning the effect of endometriosis on fertility from their doctor, whereas 31 % had discussed fertility issues with their doctor but desired further information. In contrast, only a minority (27 %) of women considered themselves well-informed on fertility preservation options. Information given by specialists on endometriosis and reproduction was considered most useful. Information mediated through patient support groups was also highly rated, whereas information given by the general gynecologist was less highly rated. The majority of women would consider assisted reproductive techniques (74 %) or adoption (70 %) in case of infertility. Interestingly, 72 % of women would undergo oocyte vitrification for fertility preservation, whereas only 37 % would resort to oocyte donation. CONCLUSION: This is the first survey to address the topic of fertility issues from the patient's perspective in women with endometriosis. The vast majority of women attach great importance to a discussion about fertility possibilities and only a minority of women consider themselves well-informed. Our results highlight the importance of addressing the issue of fertility in women with endometriosis. Special attention should be given to information and counselling about fertility preservation options since most women consider their knowledge on the topic insufficient. Knowledge and attitudes to counsel endometriosis patients on fertility issues and fertility preservation options should be included in the training curricula of gynecologists. Adequate information on reproductive aging, risk factors for infertility, and reproductive choices, including oocyte vitrification, should be incorporated into follow-up visits for endometriosis patients.

Sexual and psychological functioning in women after pelvic surgery for gynaecological cancer.

Pelvic surgery for gynecological cancer can affect sexuality through a number of anatomical, physiological and psychological mechanisms. We aimed to examine the prevalence of sexual dysfunction and psychological functioning in women who underwent pelvic surgery for gynecological cancer. Fifty women who underwent pelvic surgery for vulvar, cervical or endometrial cancer in a gynecological oncology unit completed questionnaires evaluating marital satisfaction (DAS), depression (BDI-II) and sexual functioning (SSFS and an in-house Specific Sexual Problems Questionnaire). Medical records were used to obtain disease-specific data. The control group consisted of 39 healthy age-matched control women attending an outpatient screening clinic. Significantly more women with gynaecological cancer than controls reported sexual problems (83 vs 20%), including decreased desire (76 vs 14%) and impaired vaginal lubrication (42 vs 9%). Pelvic surgery was specifically related to changed intensity of orgasm (43%), reduced vaginal sensitivity (38%), vaginal elasticity (30%), superficial dyspareunia (27%), vaginal narrowing (26%) and shortening (22%). Although no significant differences were found between either group for depression (17% vs 13%) or total quality of the partner relationship, women with a history of gynecological cancer reported significant lower marital cohesion. These results indicate that although the psychological adjustment of women who underwent pelvic surgery seems to be satisfactory, they seem to be at risk for sexual dysfunctions.

Raw material variability of an active pharmaceutical ingredient and its relevance for processability in secondary continuous pharmaceutical manufacturing.

Active Pharmaceutical Ingredients (API) raw material variability is not always thoroughly considered during pharmaceutical process development, mainly due to low quantities of drug substance available. However, synthesis, crystallization routes and production sites evolve during product development and product life cycle leading to changes in physical material attributes which can potentially affect their processability. Recent literature highlights the need for a global approach to understand the link between material synthesis, material variability, process and product quality. The study described in this article aims at explaining the raw material variability of an API using extensive material characterization on a restricted number of representative batches using multivariate data analysis. It is part of a larger investigation trying to link the API drug substance manufacturing process, the resulting physical API raw material attributes and the drug product continuous manufacturing process. Eight API batches produced using different synthetic routes, crystallization, drying, delumping processes and processing equipment were characterized, extensively. Seventeen properties from seven characterization techniques were retained for further analysis using Principal Component Analysis (PCA). Three principal components (PCs) were sufficient to explain 92.9% of the API raw material variability. The first PC was related to crystal length, agglomerate size and fraction, flowability and electrostatic charging. The second PC was driven by the span of the particle size distribution and the agglomerates strength. The third PC was related to surface energy. Additionally, the PCA allowed to summarize the API batch-to-batch variability in only three PCs which can be used in future drug product development studies to quantitatively evaluate the impact of the API raw material variability upon the drug product process. The approach described in this article could be applied to any other compound which is prone to batch-to-batch variability.

Is wheezing associated with decreased sleep quality in Sri Lankan children? A questionnaire study.

AIM: To investigate the association between wheezing and impaired sleep in Sri Lankan children, aged 6-12 years; and, to report the prevalence of asthma-related symptoms in these subjects. METHODS: The International Study of Asthma and Allergies in Childhood questionnaire and a separate sleep questionnaire were completed. RESULTS: Of 800 originally distributed questionnaires, 652 were analyzed. Wheezing was present in 89 children (14%). Within this group, 66% reported wheezing in the last 12 months. Wheezing children had a significantly higher presence of snoring, restless sleep, nocturnal awakenings and daytime tiredness. Wheezing was found to be independently associated with restless sleep (odds ratio (OR) = 2.4). There was no association between wheezing and difficulties falling asleep, nocturnal awakenings, apneas, and daytime sleepiness and tiredness. After adjusting for possible confounders, the following significant associations were present: snoring and apneas (OR = 1.6), chronic rhinitis and apneas (OR = 1.6), snoring and restless sleep (OR = 3.2), chronic rhinitis and restless sleep (OR = 2.1), and hayfever and daytime tiredness (OR = 4.3). Wheezing was related to an increased risk of snoring (OR = 2.8) and subjects with chronic rhinitis had also an increased risk of snoring (OR = 1.7), adjusting for possible confounders. CONCLUSION: The sleep of wheezing children was impaired compared with their non-wheezing peers, resulting in an increased prevalence of daytime tiredness. Upper airway symptoms, such as chronic rhinitis or hayfever, should be carefully considered in these children, as they might be responsible for these sleep problems.

Interventions to Improve the Oral Health of People with Dementia or Cognitive Impairment: A Review of the Literature.

OBJECTIVE: Oral diseases and conditions are prevalent among older people with dementia and cognitive impairment. While many interventions have been advocated for use in this population, evidence for their effectiveness is unclear. Our objective was to review systematically the content and effectiveness of interventions and implementation strategies used to improve or maintain the oral health of people with dementia or cognitive impairment. METHODS: Original studies published in English at any time until January 2015 were identified through electronic searches of the Medline, Embase, CINAHL, Scopus and Cochrane databases and hand searches of eligible studies and relevant reviews. Two investigators independently abstracted study characteristics and assessed the methodological quality of eligible studies. Results were presented as a narrative review because significant heterogeneity among included studies precluded a meta-analysis. RESULTS: The 18 included studies varied considerably in terms of size, scope and focus. Only two studies were identified that had been designed specifically for and examined exclusively in people with dementia or cognitive impairment. All studies were in residential care; none was population-based. While several studies reported positive effects, a number of methodological weaknesses were identified and the overall quality of included studies was poor. The specific outcomes targeted varied across studies but most studies focused almost exclusively on proximal clinical oral health outcomes such as levels of dental or denture plaque. Attempts to measure intervention integrity were limited and there was usually little or no effort to evaluate intervention effects over a sustained period. CONCLUSION: There is a lack of high quality evidence to support the effectiveness of oral health interventions and implementation strategies for older people with dementia or cognitive impairment. More rigorous, large scale research is needed in this area. Recommendations are provided to improve the overall quality of evaluation in this area. Emphasis must be placed on developing evidence-based, achievable and sustainable oral health strategies if the needs of people with dementia and cognitive impairment are to be met into the future.

Animal evidence for the transgenerational development of diabetes mellitus.

The mammalian fetus develops inside the uterus of its mother and is completely dependent on the nutrients supplied by its mother. Disturbances in the maternal metabolism that alter this nutrient supply from mother to fetus can induce structural and functional adaptations during fetal development, with lasting consequences for growth and metabolism of the offspring throughout life. This effect has been investigated, by several research groups, in different experimental models where the maternal metabolism during pregnancy was experimentally manipulated (maternal diabetes and maternal malnutrition) and the effect on the offspring was investigated. The altered maternal/fetal metabolism appears to be associated with a diabetogenic effect in the adult offspring, including gestational diabetes. This diabetic pregnancy in the offspring again induces a diabetogenic effect into the next generation, via adaptations during fetal development. These experimental data in laboratory animals are confirmed by epidemiological studies on infants of mothers suffering from diabetes or malnutrition during pregnancy. It can be concluded that fetal development in an abnormal intra-uterine milieu can induce alterations in the fetal metabolism, with lasting consequences for the glucose tolerance of the offspring in adult life. The most marked effect is the development of gestational diabetes, thereby transmitting the diabetogenic tendency to the next generation again. The concept of fetal origin of adult diabetes therefore is of major significance for public health in the immediate and the far future.

[Immunogenicity of biosimilars]. / Immunogeniciteit van biosimilars.

Biosimilars of more complex recombinant protein drugs, such as monoclonal antibodies and fusion proteins, are entering the market. The manufacturer should demonstrate that its product does not show any relevant differences in terms of quality characteristics, biological activity, safety and efficacy compared to the reference product, as outlined in EMA guidelines. This should be established with an extensive comparability exercise. One aspect that is subject to particular scrutiny is the immunogenicity of the biosimilar and the reference medicinal product. For three cases, one etanercept and two infliximab biosimilars, we describe how data are assessed and an opinion is reached by authorities. Not in all cases unanimity exists whether all remaining uncertainties on biosimilarity have been resolved satisfactorily before marketing authorisation. The Dutch Medicines Evaluation Board therefore emphasises that even after marketing authorisation, biosimilars and other biologicals should be properly monitored.

Long-term effect of diabetes and pregnancy in the rat.

Islet hyperplasia and B-cell degranulation were found in the fetuses of the third generation from mothers (second generation) born to a diabetic mother (first generation) regardless of the origin of the father, while pancreatic islets were normal in fetuses from control mothers, even when the father was an offspring of a diabetic mother. These data support the hypothesis that in our experimental model overstimulation of the fetal endocrine pancreas results in long-term consequences to the third generation.

Metabolic alterations in adulthood after intrauterine development in mothers with mild diabetes.

We studied the long-term effects of maternal diabetes mellitus on the offspring of experimentally induced diabetic Wistar rats. When stressed by an intravenous glucose load, the adult female offspring had impaired glucose tolerance and developed gestational diabetes mellitus when pregnant. Our results show that even mild diabetes mellitus induces an abnormal intrauterine milieu that causes morphological and functional changes in fetal development with consequences for later life.

In vivo glucose utilization by individual tissues in virgin and pregnant offspring of severely diabetic rats.

Adult offspring of diabetic rats or SDF rats are characterized by insulin resistance in the liver and extrahepatic tissues; this insulin resistance does not worsen during pregnancy. In this study, we determined the glucose metabolic index in tissues of anesthetized virgin and pregnant control and SDF rats in basal conditions and during a euglycemic hyperinsulinemic clamp. Tissues comprised insulin-sensitive tissues (five skeletal muscles, diaphragm, and periovarian white adipose tissue) and control tissues (duodenum and cerebrum). In addition, this study measured the GMI of placenta and fetuses. In basal conditions, SDF rats showed a slight decrease (9-29%) in the GMI of skeletal muscles compared with control rats; it was not altered by pregnancy in any of the tissues. During physiological hyperinsulinemia, virgin SDF rats exhibited a 25-70% decrease in the GMI of skeletal muscles compared with control rats; this decrease was not observed in diaphragm, or in adipose tissue in which the GMI was found to be increased. During pregnancy, SDF rats did not show an additional drop in the GMI of skeletal muscles, whereas the GMI of both skeletal muscles and adipose tissue was clearly diminished (25-60%) in control rats. The GMI of skeletal muscles was therefore comparable in pregnant control rats and SDF rats. The placental, but not fetal, GMI was increased by 24% during hyperinsulinemia in control rats; the placental and fetal GMIs, in basal and hyperinsulinemic conditions, were similar in control rats and SDF rats. In conclusion, skeletal muscles, but not white adipose tissue, are involved in the peripheral insulin resistance of the SDF rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Endocrine pancreas in the offspring of rats with experimentally induced diabetes.

At birth newborn rats from mothers with experimentally induced diabetes show hypertrophy and degranulation of the pancreatic islets. With birth the maternal hyperglycaemic stimulus is removed and during the lactation period the overstimulated B cells can restore their normal secretory activity. The increase of B-cell mass, however, remains retarded for several weeks. By adulthood the endocrine pancreas of offspring from mildly diabetic mothers seems to have recovered from the influence of the abnormal intra-uterine milieu, at least as judged by morphometric examination. In offspring from severely diabetic mothers an increased secretory activity of the individual B cells might be responsible for their sustained hypoglycaemia.

Rat foetal endocrine pancreas in experimental diabetes.

The endocrine pancreas of foetuses and newborn rats of experimental diabetic mothers showed morphological and ultrastructural changes. Islet hypertrophy and beta cell hyperplasia were constantly present, but the beta cells of foetuses of severely diabetic mothers were degranulated. The ultrastructural changes indicated hyperfunction in the beta cells of foetuses of experimental diabetic mothers. The morphological changes mentioned were similar to those seen in human diabetic pregnancy.

Absence of pregnancy-induced alterations in tissue insulin sensitivity in the offspring of diabetic rats.

We have previously demonstrated insulin resistance in the liver and peripheral tissues of the adult offspring of rats made diabetic with streptozotocin (SDF rats). In this study, a euglycaemic hyperinsulinaemic clamp was used to test the hypothesis that insulin resistance is further aggravated during pregnancy in SDF rats. Normal pregnancy was accompanied by a decrease in the sensitivity of the liver and peripheral tissues to insulin, with a normal responsiveness to insulin. In SDF rats no further decrease in the sensitivity of peripheral tissues to insulin occurred during pregnancy when compared with non-pregnant rats, and the dose-response curves of the glucose metabolic clearance rate during hyperinsulinaemia were similar in pregnant control and pregnant SDF rats. There was, however, a modest decrease in the sensitivity of the liver to insulin during pregnancy in SDF rats. The normal increase in plasma insulin levels during pregnancy was blunted in SDF rats: this resulted in increased glucose levels in maternal and fetal rats and increased fetal insulin concentrations, features compatible with mild 'gestation diabetes'. In conclusion, gestational diabetes develops in pregnant SDF rats, although there is no further deterioration in peripheral insulin resistance.

Morphological changes in the endocrine pancreas in pregnant rats with experimental diabetes.

This present study has demonstrated that during normal pregnancy in the rat the number of beta-cells is increased (hyperplasia) and the volume of the individual beta-cells is increased (hypertrophy). During experimental diabetes, however, the endocrine pancreas has an impaired capacity to compensate during pregnancy. In the experimental diabetic pregnant rat the beta-cells cannot replicate due to the unfavourable metabolic environment. This could reflect the complications caused by diabetes during human pregnancy.

Effects of treatment with progesterone and oestradiol-17 beta on the endocrine pancreas in ovariectomized rats: ultrastructural variations in the B cells.

The effects of progesterone and/or oestradiol treatment on the ultrastructural appearance of the pancreatic B cells has been studied in ovariectomized Wistar rats. A morphometric examination of the numberical density of dark and high granules in the B cells was therefore performed in each group of experimental rats as well as in control (olive oil-injected) rats. In the oestradiol-treated rats, and especially in the rats with combined oestradiol/progesterone treatment, the proportions of light and dark granules in the pancreatic B cells changed, compared with control values, in favour of the light granules. This increase in light granule content was comparable to changes in B cells during a pregnancy and it is suggested that the secretory activity of the B cells increases during pregnancy in a manner similar to that seen during oestradiol treatment.

Intra-uterine transmission of disease.

Fetal development is dependent on maternal supply of fuels and building blocks. Disturbed maternal metabolism or inappropriate maternal nutrition confronts the fetus with an unfavourable intra-uterine milieu. Structural and functional adaptations occur during development and maturation of organs. Consequences of these fetal alterations persist postnatally and may result in metabolic alterations throughout life. Gestational diabetes can occur in these offspring and transmit the effect to the next generation. These alterations in fetal development can be associated with fetal macrosomia (maternal diabetes) or fetal growth-restriction (maternal/fetal malnutrition). The relation between birth weight and later metabolic disease therefore is U-shaped. Adult metabolic condition is thus to a considerable extent programmed in utero, fetal and neonatal weight being symptoms of disturbed fetal development. This concept of intra-uterine programming of disease is illustrated with a review of epidemiological human studies and experimental animal studies.

Pancreatic islet transplantation in diabetic pregnant rats prevents acquired malformation of the ventromedial hypothalamic nucleus in their offspring.

Exposure to a diabetic intrauterine environment leads to diabetogenic disturbances throughout later life in rats. This is accompanied by a fetally acquired dysplasia of the ventromedial hypothalamic nucleus (VMN) which is decisively involved in the regulation of metabolism. We investigated whether malformation of the VMN is preventable by normalization of gestational hyperglycaemia. Correction of hyperglycaemia in pregnant streptozotocin-diabetic rats was achieved by pancreatic islet transplantation. The number of neurons in the VMN was significantly reduced in adult offspring of non-treated, sham-transplanted mother rats (P<0.05), but did not differ between offspring of islet-transplanted mother rats and offspring of control mothers. In conclusion, prevention of VMN malformation in offspring of islet-transplanted diabetic mothers might be co-responsible for normalization of their glucose homeostasis during life.

Fetal growth restriction and consequences for the offspring in animal models.

OBJECTIVE: In the present review we discuss rat models in which intra-uterine growth restriction is obtained through pharmacological (streptozotocin), dietary (global food restriction, low protein diet), or surgical (uterine artery ligation) manipulation of the maternal animal. METHODS: A MEDLINE search was performed on rat models of intrauterine growth restriction (IUGR), ie, streptozotocin, food restriction, low protein diet, or uterine artery ligation and pregnancy and fetal programming, long-term effects or adult offspring. RESULTS: We address the impact of the different maternal conditions for the fetal and neonatal development. The rat models we concentrate on were all associated with fetal hypoinsulinemia and intrauterine growth restriction. Both fetus and neonate adapt to the altered perinatal environment. Some of these adaptations may predispose the offspring to the development of insulin resistance, cardiovascular disease, obesity, and even overt diabetes in later life. CONCLUSION: The adaptations of the fetal metabolism to the altered intrauterine environment have consequences for the offspring, persisting into adulthood and into the next generation.